The project's goal is to refine antemortem diagnosis of frontotemporallobar degeneration (FTLD) and related disorders by distinguishing them from Alzheimer's disease (AD), by improving early diagnosis and by differentiating patients with ubiquitin inclusions from those with tau inclusions. By the end of year 10 of the PPG this project will have obtained novel assessment on 107 AD, 131 FTD, 67 SD, 56 PNFA, 43 CBD, 30 PSP, 59 ALS, and 89 controls. Neuropathology will be completed in 37 AD, 64 FTD, 25 SD, 23 PNFA, 23 CBD, 23 PSP and 27 ALS patients. By exploring clinical pathological correlates in these populations the project will accomplish the following aims: 1. Refine diagnostic approaches to FTD, PNFA, SD, CBD, and PSP in order to improve separation of these patient groups during life from patients with AD. This aim will be facilitated by the use of amyloid imaging with the Pittsburgh-compound-B (PIB). Also, genomics and proteomics will be preliminarily explored as tools for differential diagnosis of FTD, PNFA, SD, CBD and PSP from each other, and from AD. 2. Explore the earliest changes in FTD patients with a clinical dementia rating (CDR) score of 0.5, and ALS patients (many will have early FTD). This aim will be tested using novel paradigms that capture social, emotional and imaging domains through the Clinical and Administrative Core and in projects 2, 3 and 4. Also, genomics and proteomics will be explored as potential markers of early FTD or FTD-ALS. 3. Identify syndromes that best predict FTLD-T vs. FTLD-U as defined at pathology. The aim will be performed by analyzing data collected through the Clinical and Administrative Core and projects 2 and 3. Also, genomic and proteomic profiles will be explored in these populations.